We have discovered a series of chemical compounds that delay the onset of age-related pathology and extend lifespan. These compounds were identified in focused chemical screens and high throughput screens of both synthetic compounds and natural products. Here we propose to identify the mechanism of lifespan extension with a focus on vitamin D which we have shown maintains protein homeostasis and extends lifespan in C. elegans. This will uncover novel mechanisms for interventions in aging and age-related disease.